Human and feline immunodeficiency viruses (HIV and FIV) cause a similar disease syndrome in their respective host species. This disease syndrome evolves over years in three consecutive stages; acute, asymptomatic, and terminal. The acute state is referred to as "mononucleosis-like illness," while the terminal state is called AIDS in people and AIDS-like disease in cats. Of these 3 stages, the acute stage is the most important. It is during this acute illness that the first major decrease in CD4+ T cells occurs and when the life-long pattern of viral persistence is established. Many of the events in the terminal stage of infection are merely recapitulations of these early events, eg.g., viremia, accelerated decline in CD4+ T cells, lymphadenopathy, cytopenias. Certain biologic events that occur during acute illness are of particular importance: 1) the abrupt and permanent decline in CD4+ T cells, and 2) the establishment of a persistent infection. Therefore, the goal of the project is to study, in greater depth, certain biologic phenomena that have been observed during the acute stages of both FIV and IIIV infections, and to relate these events to immunodeficiency virus- mediated CD4+ T cell depletion and persistence. To this end, the specific aims of the study are: 1) To determine whether the primary immune response to lentivirus infections favors viral persistence over viral recovery as determined by the profile of cytokine responses in lymphoid organs. 2) Cyclosporine A treatment during the acute symptomatic and chronic asymptomatic stages of FIV infection and its comparative effects on the TH1 and TH2 pathway of cytokine activation. 3) To determine the role of TNF-alpha in the pathogenesis of FIV-induced disease. 4) To study the relation of early thymic lesions to the CD4+ T cell depletion that begins during the acute stage of FIV (and IIIV) infections. 5) To determine the significance of autoimmune phenomena that appear during the acute stages of FIV (and IIIV) infections.